Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.1624 Discontinue certolizumab pegol if serious infection occurs.16 Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.1624

Malignancy

Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.1925 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

REMS:

FDA approved a REMS for certolizumab pegol to ensure that the benefits outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Following reconstitution, draw up each 400-mg dose into 2 syringes, each containing 200 mg, and administer by sub-Q injection into separate sites on the thighs or abdomen using 23-gauge needles.1

Reconstituted solution intended for use under the guidance and supervision of a clinician.1 Certolizumab pegol solution supplied in prefilled syringes may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training.1

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept.1523 (See Specific Drugs and Laboratory Tests under Interactions.)

Patients >65 years of age, with comorbid conditions, and/or receiving concomitant therapy with immunosuppressive agents (e.g., corticosteroids, methotrexate) may be at increased risk of infection.124

Do not initiate certolizumab pegol in patients with active infections, including clinically important localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.124

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.124 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to certolizumab pegol therapy.1 Consider antimycobacterial therapy prior to initiating certolizumab pegol in patients with a history of latent or active tuberculosis for whom adequate antimycobacterial treatment is unconfirmed, and in patients with a negative tuberculin skin test who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.1 Strongly consider tuberculosis in patients who develop new infections during therapy, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.1

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.6 Whenever feasible, consult specialist in fungal infections.6

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.19 Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).19 Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.1 FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.9

Hepatosplenic T-cell lymphoma (a rare, aggressive, usually fatal T-cell lymphoma) reported mainly in adolescents and young adults with Crohn’s disease or ulcerative colitis receiving TNF blocking agents and/or thiopurine analogs (mercaptopurine or azathioprine).25 Most of the patients received a combination of immunosuppressive agents, including TNF blocking agents and thiopurine analogs.25

In controlled studies, lymphoma was reported more frequently in patients receiving certolizumab pegol or other TNF blocking agents than in control patients.1 Patients with Crohn’s disease, rheumatoid arthritis, and other chronic inflammatory diseases, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma;1925 may be difficult to measure added risk of TNF-blocking agents, azathioprine, and/or mercaptopurine.25

In clinical studies of certolizumab pegol, rate of malignancies other than nonmelanoma skin cancer was 0.5 or 0.6 per 100 patient-years in patients receiving certolizumab pegol or placebo, respectively; however, the role of certolizumab pegol use in the development of malignancies not fully determined.19

Acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.19 Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.9 FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.19

In controlled studies of other TNF blocking agents in adults at increased risk of malignancies (e.g., patients with COPD and a history of heavy smoking, patients with Wegener’s granulomatosis receiving concomitant cyclophosphamide), a greater proportion of malignancies occurred in patients receiving the TNF blocking agent compared with control patients.2829

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.925

Carefully consider risks and benefits of TNF blocking agents, especially in adolescents and young adults and especially in the treatment of Crohn’s disease or ulcerative colitis.25

Other Warnings/Precautions

Cardiovascular Effects

Worsening CHF and new-onset CHF reported in patients receiving TNF blocking agents; certolizumab pegol not studied in patients with CHF.1 If used in patients with CHF, caution and careful monitoring recommended.1

Sensitivity Reactions

HBV Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of this virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).15 Fatalities reported.1 Use of multiple immunosuppressive agents may contribute to HBV reactivation.1

Screen at-risk patients prior to initiation of therapy.1 Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.1 Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.1 Discontinue certolizumab pegol and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.1 Not known whether certolizumab pegol can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.1

Immunologic Reactions and Antibody Formation

Antibodies to certolizumab pegol may develop.1 Incidence of antibody formation was lower in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate) than in those not receiving immunosuppressive agents at baseline.1

Antibody formation associated with lower plasma drug concentrations and reduced efficacy in patients with rheumatoid arthritis.1 In patients with Crohn’s disease, no apparent association between antibody development and efficacy or adverse events.1

Immunization

Immunosuppression

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including certolizumab pegol.19 Most patients experienced improvement following discontinuance of the TNF blocking agent.9

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.9

Advice to Patients

A copy of the manufacturer’s patient information (medication guide) for certolizumab pegol should be provided to all patients with each prescription of the drug.19 Importance of advising patients about potential benefits and risks of certolizumab pegol.192425 Importance of patients reading the medication guide prior to initiation of therapy and before each injection of the drug.12425

Importance of instructing patient and/or caregiver regarding proper dosage and administration of certolizumab pegol, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.1

Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, and other malignancies with use of TNF blocking agents.1925 Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease.925 Importance of promptly informing clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; hepatomegaly or splenomegaly) occur.925

Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.925

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurrent infections.1624

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information. (See Cautions.)1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Certolizumab Pegol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

2 vials (200 mg each)

Cimzia (available as kit with sterile water for injection diluent, needles, syringes, and alcohol swabs)